Project Summary Clinical neural, cardiac and neuromuscular modulation devices can alter the bioelectric signal flow within a biological circuit for patient benefit. Successful examples include deep brain stimulators for the treatment of Parkinson?s disease and tremor, and spinal cord stimulators for pain. Despite some impressive results collected from the intended patient populations, biological modulation still faces several major challenges. For example, the direct biological integration still has issues such as tissue lesions during insertion, persistent irritation, and engineering difficulties in thermal management, power delivery, and external control. Over the past ten years, there has also been a strong interest in improving the specificity of treatment through the use of optogenetics technologies, although their clinical use still has hurdles. Here, I propose a new silicon micro-gel based platform for wireless modulation of single cells, engineered tissues, and neuromuscular tissues in vivo. The silicon micro-gels can be delivered by injection and subsequent self-assembly onto plasma membranes. Through topography designs and surface modifications, these silicon micro-gels will be soft, adhesive and biocompatible. When activated by light pulses, they will trigger a transient charge or temperature imbalance in the ionic solution, which cause the excitable cells to fire. Our preliminary results already show the successful synthesis of one simplest form of the proposed silicon micro-gels. Significantly, our initial data also demonstrate a photothermal mechanism, which enables wireless and deterministic modulation of neural activities. The initial synthetic success and the neuronal control represent an excellent starting point for the proposed research. I expect that successful completion of our work will result in silicon-based wireless photoelectric or photothermal modulation components for cells and tissues, with better than micrometer spatial resolution and microsecond temporal resolution. The knowledge gleaned from this work would lead to an injectable form of wireless semiconductor implants for restoring biological function lost. I also believe that it has the potential to make breakthrough and paradigm shifts in biomedical research through the establishment of powerful new tools for understanding the behavior of interacting cellular networks, the development of sophisticated, electrically- and thermally-based cell/tissue interfaces for prosthetics and other medical devices, and the creation of new hybrid biomaterials that might open-up completely new areas or applications, such as in hybrid cellular information processing systems.